2-Hydroxy-4-methylthiobutyric acid and its salts have been used for a long time in animal nutrition as a replacement for methionine because they have the advantage of having a liquid form, which facilitates their use by feed producing companies.
The preparation of 2-hydroxy-4-(methylthio)butanoic acid by a chemical route has been known for a long time. European patent nos. EP-142 488 and 143 000 describe the hydrolysis of 2-hydroxy-4-methylthio-hydroxybutyronitrile (HMTBN) by a two-stage process. The first stage consists in bringing the 2-hydroxy-4-methylthiobutyronitrile into contact with a strong inorganic acid such as hydrochloric or sulphuric acid. In a subsequent stage, after dilution with water, the hydrolysis is completed at a higher temperature. The 2-hydroxy-4-(methylthio)butanoic acid is then extracted with an organic solvent which is not very miscible with water, such as a ketone, preferably methyl isobutyl ketone, and then the solvent is removed by evaporation. This type of process, which is used industrially, nevertheless has some disadvantages. In particular, it produces a molar quantity of ammonium sulphate, at least equal to the molar quantity of nitrile introduced, which has to be removed, thus generating an industrial waste which runs counter to environmental protection policies. This process also requires the use of large quantities of solvent which must be recycled.
Other processes such as those described in U.S. Pat. No. 3,773,927 and 4,353,924 consist in hydrolysing 2-hydroxy-4-methylthio-butyronitrile with hydrochloric acid and then concentrating the medium with separation of the ammonium chloride formed. The salt obtained is as difficult to remove as the preceding salt and, furthermore, the acid obtained has a strong color.
A process for the chemical hydrolysis of methylthio-hydroxypropionitrile which consists, as above, in carrying out a hydrolysis in a sulphuric medium, is described in European Patent No. 330 521. The mixture is partially neutralized with ammonium hydroxide followed by a two-phase separation. The organic phase contains most of the 2-hydroxy-4-methylthiobutyric acid and the aqueous phase contains most of the ammonium sulphate produced. The organic solution, after evaporation of the water which it contains, is filtered so as to recover the dissolved ammonium sulphate. The 2-hydroxy-4-methylthiobutyric acid is then diluted with a small quantity of water and stabilized with a small quantity of sulphuric acid. The aqueous solution, after elimination of the water, makes it possible to obtain ammonium sulphate which is directly marketable. This process partly overcomes the disadvantages of the prior art process with regard to the use of organic solvents, but does not in any way solve the problems linked to the discharge of the inorganic salts.
Among the patents relating to the salts of 2-hydroxy-4-methylthiobutyric acid, there may be mentioned U.S. Pat. Nos. 2,745,745, 2,938,053, and 3,175,000, which relate to calcium and/or ammonium salts. The mixture obtained by hydrolysis of the 2-hydroxy-4-methylthiobutyronitrile is treated with calcium hydroxide or carbonate. The calcium sulphate is then precipitated, releasing the ammonium hydroxide which forms the ammonium salt of 2-hydroxy-4-methylthiobutyric acid. Here again, the problem consists in removing the calcium sulphate which remains.
A process which consists in carrying out a hydrolysis and an extraction with an organic solvent, as in the first document cited above, followed by a neutralization of the organic solution with ammonium hydroxide is also described in International Patent Application WO 96/01808. This process, as in the majority of the processes previously described, leads to the formation of at least one mole of ammonium sulphate or chloride per mole of nitrile introduced and requires the recycling of large quantities of organic solvent. Thus, it is not possible to obtain a solution of ammonium salt of 2-hydroxy-4-methylthiobutyric acid at an industrially advantageous cost.
The use of a nitrilase as a catalyst for the hydrolysis of a nitrile group into a carboxyl group is disclosed in U.S. patent application Ser. No. 08/809,184, filed Mar. 20, 1997 now U.S. Pat. No. 5,814,497. This process, however, is not capable of being used on an industrial scale given the insufficient activity of the microorganisms which synthesize these nitrilases.